Mapping of microsatellite instability in endoscopic normal colon

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Genomic instability in colorectal cancer (CRC) manifests as microsatellite instability (MSI) or chromosomal instability.
• MSI is a key biomarker in CRC development and progression.

Purpose of the Study:

• To investigate the presence and frequency of MSI in MLH1 and MSH2 genes within normal colon tissues and polyps.
• To assess the correlation between MSI status and family history of cancer.

Main Methods:

• Colonoscopy was performed on 102 subjects, with tissue samples collected from four colonic segments.
• DNA samples were analyzed for MSI status using the Bethesda consensus panel criteria.
• Family history of cancer was recorded for all participants.

Main Results:

• 32% of individuals exhibited high MSI (MSI-H), 20% had low MSI (MSI-L), and 48% were microsatellite stable.
• MSI was detected in endoscopically normal colon tissue, particularly in individuals with a family history of CRC.
• Significant differences in MSI marker frequencies were observed (p=0.003), with D17S250 being the most frequent positive marker.

Conclusions:

• MSI is present in apparently normal colon tissue, suggesting its role in early stages of CRC.
• MSI analysis of DNA mismatch repair genes holds potential for early CRC detection.
• High frequencies of MSI in normal colon may lead to false positives in molecular screening tests.